1. Technical Field
The present invention relates to an antibody against an amyloid precursor protein signal peptide. The invention also relates to a monoclonal antibody against the amyloid precursor protein signal peptide and a hybridoma producing the same.
2. Related Art
Peptides per se are widely and generally known to have various functions, such as hormone and neurotransmitter, in vivo. Among such peptides, peptides playing a plurality of physiological roles have been reported in recent years. Previously, a short peptide region called a signal peptide had been considered to be only responsible for translocating a newly synthesized protein to the endoplasmic reticulum. However, other physiological roles have been reported one after another in recent years (Trends in Cell Biology, 1998, vol. 8, pp. 410-415).
For example, a portion of the calreticulin signal peptide has been demonstrated to be presented on the cell surface by major histocompatibility complex (MHC) (Science, 1992, vol. 255, pp. 1264-1266). The physiological significance of such phenomenon is considered to be probably a part of a mechanism for monitoring the expression level of the intracellular protein or the production proportion of the normal signal peptide. However, no conclusion has been reached.
It has also been shown that a portion of the calcitonin signal peptide is presented on the surface of non-small cell lung cancer cells by MHC and cytotoxic T cells recognize the signal peptide as an epitope, which has been expected to be useful for the development of a cancer vaccine (Proceedings of the National Academy of Sciences of the United States of America, 2008, vol. 29, no. 105, pp. 10119-10124).
As described above, signal peptides have been each shown to not only be a mere signal guiding a protein to the endoplasmic reticulum but also have a new physiological/pathological significance. Thus, there is no denying that signal peptides that have not been characterized well could be involved as a factor responsible for some kind of important physiological phenomenon, for example, unexplained refractory diseases.
An example of such refractory diseases includes Alzheimer's disease. Alzheimer's disease is advanced dementia having pathological characteristics such as neuronal loss, amyloid β accumulation, and neurofibrillary change in the brain. Based on these pathological characteristics, the hypothesis prevails that amyloid β is a primary cause, and methods for diagnosing/treating Alzheimer's disease have been studied for many years. However, not only a treatment method but also a pathogenic mechanism has not yet been determined. With the foregoing current circumstances in view, the opinion is recently arising that the amyloid β theory may be wrong (Nature, 2008, vol. 456, pp. 161-164). In addition, there is a report suggesting that a factor other than amyloid β is involved in the onset of Alzheimer's disease.
It is disclosed that the region from the N-terminus to the 286th residue of the amyloid precursor protein promotes the degeneration of neurons, and the authors address that it has the possibility of providing a causative substance for Alzheimer's disease other than amyloid β (Nature, 2009, vol. 457, pp. 981-989).
The literature (Nature, 2009, vol. 457, pp. 981-989) discloses that the protein from the N-terminus to the 286th residue of the amyloid precursor protein promotes neuronal degeneration. However, it does not disclose which portion of the region is the essential portion responsible for the neuronal degeneration.